Secondary Analysis of COLOFOL Trial Shows No Survival Benefit from Intensive Post-Surgery Follow-Up in Stage II/III Colorectal Cancer

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A follow-up analysis of the COLOFOL trial (NCT00225641) showed that differences in the frequency of postoperative follow-up regimens did not produce any significant improvements in 10-year overall mortality or in colorectal cancer–specific mortality among patients with stage II or III colorectal cancer.^1,2 The study findings, published by the Journal of the American Medical Association (JAMA), indicate a limited survival benefit from intensive monitoring among this patient population, according to the authors.

“Among patients with stage II or III colorectal cancer, more frequent follow-up testing with (computed tomography [CT]) scans and (serum carcinoembryonic antigen [CEA]) testing did not result in a significant reduction in 10-year overall mortality or colorectal cancer–specific mortality,” the study authors wrote. “The results of this trial should be considered as the evidence base for updating clinical guidelines.”¹

It is common clinical practice to conduct intensive follow-up in patients following curative surgery for colorectal cancer; however, there are limited data showing a survival benefit from this practice. The authors of the COLOFOL trial, published by JAMA in 2018, sought to evaluate overall mortality, colorectal cancer–specific mortality, and colorectal cancer–specific recurrence rates among patients with stage II or III colorectal cancer.³ These patients were randomly assigned to undergo two alternative schedules for follow-up testing with high- or low-frequency CT and CEA testing following surgery.

The results of the 2018 analysis show that among 2509 patients, the five-year overall mortality rate in the high-frequency cohort was 13.0% (161/1253) vs. 14.1% (174/1256) in the low-frequency cohort (risk difference, 1.1% [95% CI, −1.6% to 3.8%]; P = .43). Five-year colorectal cancer–specific mortality rate was 10.6% in the high-frequency cohort (128/1248) vs. 11.4% (137/1250) in the low-frequency cohort (risk difference, 0.8% [95% CI, −1.7% to 3.3%]; P = .52). Additionally, the colorectal cancer–specific recurrence rate was 21.6% (265/1248) in the high-frequency cohort vs. 19.4% (238/1250) in the low-frequency cohort (risk difference, 2.2% [95% CI, −1.0% to 5.4%]; P = .15).³

“In this trial of more than 2500 patients with colorectal cancer who underwent surgery with curative intent, no significant rate differences in 5-year overall mortality or colorectal cancer–specific mortality were found when the intensity of postoperative colorectal cancer follow-up was increased from 2 to 5 examinations during the 3 years after surgery and with 5 years of follow-up,” the study authors wrote. “In the high-intensity group, colorectal cancer–specific recurrence was detected earlier, but this did not translate into a reduced mortality rate.”³

The posttrial prespecified secondary analysis of the randomized COLOFOL trial included 2456 patients with stage II or III colorectal cancer. Follow-up testing with CT scans and CEA screening was conducted on either five or two occasions. The primary outcomes were 10-year overall mortality rates and colorectal cancer–specific mortality rates.

Among 2509 patients in the intention-to-treat analysis, 2456 (97.9%) were included in the posttrial evaluation (median age, 65 years [IQR, 59-70 years]; 1355 male patients [55.2%]). The results showed a 10-year overall mortality rate of 27.1% in the high-frequency cohort (333 of 1227; 95% CI, 24.7%-29.7%) vs. 28.4% in the low-frequency cohort (349 of 1229; 95% CI, 26.0%-31.0%). Ten-year colorectal cancer–specific mortality in the high-frequency group was 15.6% (191 of 1227; 95% CI, 13.6%-17.7%) vs. 16.0% (196 of 1229; 95% CI, 14.0%-18.1%) in the low-frequency cohort.¹

“Although neither trial could prove any survival benefit by more frequent follow-up in the randomized study groups, it might be that some high-risk subgroups could benefit,” the study authors concluded. “However, none of the trials were designed to evaluate this outcome, although the subgroup analysis of stage III tumors and an ad hoc analysis of the risk group with elevated CEA levels preoperatively and/or postoperatively showed no support to this assumption. Specially designed studies are needed to investigate this question.”¹

References

1. Sørensen HT, Horváth-Puhó E, Petersen SH, Wille-Jørgensen P, Syk I, COLOFOL Study Group. More vs Less Frequent Follow-Up Testing and 10-Year Mortality in Patients With Stage II or III Colorectal Cancer: Secondary Analysis of the COLOFOL Randomized Clinical Trial. JAMA Netw Open. 2024;7(11):e2446243. doi:10.1001/jamanetworkopen.2024.46243

2. Assessment of Frequency of Surveillance After Curative Resection in Patients With Stage II and III Colorectal Cancer. ClinicalTrials.gov. Updated December 22, 2015. Accessed November 22, 2024. https://clinicaltrials.gov/study/NCT00225641

3. Wille-Jørgensen P, Syk I, Smedh K, et al. Effect of More vs Less Frequent Follow-up Testing on Overall and Colorectal Cancer–Specific Mortality in Patients With Stage II or III Colorectal Cancer: The COLOFOL Randomized Clinical Trial. JAMA. 2018;319(20):2095–2103. doi:10.1001/jama.2018.5623